Molecular Structure-Based Screening of the Constituents of Calotropis procera Identifies Potential Inhibitors of Diabetes Mellitus Target Alpha Glucosidase

Diabetes mellitus is a disorder characterized by higher levels of blood glucose due to impaired insulin mechanisms. Alpha glucosidase is a critical drug target implicated in the mechanisms of diabetes mellitus and its inhibition controls hyperglycemia. Since the existing standard synthetic drugs have therapeutic limitations, it is imperative to identify new potent inhibitors of natural product origin which may slow carbohydrate digestion and absorption via alpha glucosidase. Since plant extracts from Calotropis procera have been extensively used in the treatment of diabetes mellitus, the present study used molecular docking and dynamics simulation techniques to screen its constituents against the receptor alpha glucosidase. Taraxasterol, syriogenin, isorhamnetin-3-O-robinobioside and calotoxin were identified as potential novel lead compounds with plausible binding energies of −40.2, −35.1, −34.3 and −34.3 kJ/mol against alpha glucosidase, respectively. The residues Trp⁴⁸¹, Asp⁵¹⁸, Leu⁶⁷⁷, Leu⁶⁷⁸ and Leu⁶⁸⁰ were identified as critical for binding and the compounds were predicted as alpha glucosidase inhibitors. Structurally similar compounds with Tanimoto coefficients greater than 0.7 were reported experimentally to be inhibitors of alpha glucosidase or antidiabetic. The structures of the molecules may serve as templates for the design of novel inhibitors and warrant in vitro assaying to corroborate their antidiabetic potential.     

Yield loss at the different growth stages in soybean due to insect pests in Ghana

Insecticide protection at the vegetative, reproductive or both vegetative and reproductive (complete) crop growth stages and untreated control was used to assess yield loss due to insect pests at the different growth stages of soybean in Ghana from 2007–2009. The objectives were to determine the economic importance of the two major insect pest guilds in soybean, viz. defoliators and pod feeders, and when to apply control measures for maximum benefit. The defoliators recorded were Podagrica spp., Ootheca mutabilis (Shalberg), Zonocerus variegatus L., Sylepta derogata F., Spodoptera littoralis Boisduval, Amsacta spp. and Helicoverpa armigera Hübner. The pod feeders recorded were the pod-sucking bugs (PSBs) Riptortus dentipes F., Thyanta sp. Aspavia armigera F., Nezara viridula L. and Dysdercus völkeri Schmidt. Generally, insect densities, pod and seed damage were lower while seed yields were significantly greater and similar in plots that were protected at the reproductive stage against PSBs and those protected at both vegetative and reproductive stages. Yield loss ranged between 25.8 and 42.8% in untreated plots, 11.1 and 34.3% in plots that were protected at the vegetative stage, and 5.2 and 11.3% in plots that were protected at the reproductive stage. There was a consistent negative correlation between yield and numbers of PSBs as well as pod and seed damage. These results showed that PSBs that attack soybean at the reproductive stage were the most important insect pests limiting soybean yield in Ghana.     

The Economic Burden of Meningitis to Households in Kassena-Nankana District of Northern Ghana

Objective

To estimate the direct and indirect costs of meningitis to households in the Kassena-Nankana District of Ghana.

Methods

A Cost of illness (COI) survey was conducted between 2010 and 2011. The COI was computed from a retrospective review of 80 meningitis cases answers to questions about direct medical costs, direct non-medical costs incurred and productivity losses due to recent meningitis incident.

Results

The average direct and indirect costs of treating meningitis in the district was GH¢152.55 (US$101.7) per household. This is equivalent to about two months minimum wage earned by Ghanaians in unskilled paid jobs in 2009. Households lost 29 days of work per meningitis case and thus those in minimum wage paid jobs lost a monthly minimum wage of GH¢76.85 (US$51.23) due to the illness. Patients who were insured spent an average of GH¢38.5 (US$25.67) in direct medical costs whiles the uninsured patients spent as much as GH¢177.9 (US$118.6) per case. Patients with sequelae incurred additional costs of GH¢22.63 (US$15.08) per case. The least poor were more exposed to meningitis than the poorest.

Conclusion

Meningitis is a debilitating but preventable disease that affects people living in the Sahel and in poorer conditions. The cost of meningitis treatment may further lead to impoverishment for these households. Widespread mass vaccination will save households'' an equivalent of GH¢175.18 (US$117) and impairment due to meningitis.     

Rotavirus vaccine efficacy up to 2 years of age and against diverse circulating rotavirus strains in Niger: Extended follow-up of a randomized controlled trial

BackgroundRotavirus vaccination is recommended in all countries to reduce the burden of diarrhea-related morbidity and mortality in children. In resource-limited settings, rotavirus vaccination in the national immunization program has important cost implications, and evidence for protection beyond the first year of life and against the evolving variety of rotavirus strains is important. We assessed the extended and strain-specific vaccine efficacy of a heat-stable, affordable oral rotavirus vaccine (Rotasiil, Serum Institute of India, Pune, India) against severe rotavirus gastroenteritis (SRVGE) among healthy infants in Niger.Methods and findingsFrom August 2014 to November 2015, infants were randomized in a 1:1 ratio to receive 3 doses of Rotasiil or placebo at approximately 6, 10, and 14 weeks of age. Episodes of gastroenteritis were assessed through active and passive surveillance and graded using the Vesikari score. The primary endpoint was vaccine efficacy of 3 doses of vaccine versus placebo against a first episode of laboratory-confirmed SRVGE (Vesikari score ≥ 11) from 28 days after dose 3, as previously reported. At the time of the primary analysis, median age was 9.8 months. In the present paper, analyses of extended efficacy were undertaken for 3 periods (28 days after dose 3 to 1 year of age, 1 to 2 years of age, and the combined period 28 days after dose 3 to 2 years of age) and by individual rotavirus G type. Among the 3,508 infants included in the per-protocol efficacy analysis (mean age at first dose 6.5 weeks; 49% male), the vaccine provided significant protection against SRVGE through the first year of life (3.96 and 9.98 cases per 100 person-years for vaccine and placebo, respectively; vaccine efficacy 60.3%, 95% CI 43.6% to 72.1%) and over the entire efficacy follow-up period up to 2 years of age (2.13 and 4.69 cases per 100 person-years for vaccine and placebo, respectively; vaccine efficacy 54.7%, 95% CI 38.1% to 66.8%), but the difference was not statistically significant in the second year of life. Up to 2 years of age, rotavirus vaccination prevented 2.56 episodes of SRVGE per 100 child-years. Estimates of efficacy against SRVGE by individual rotavirus genotype were consistent with the overall protective efficacy. Study limitations include limited generalizability to settings with administration of oral polio virus due to low concomitant administration, limited power to assess vaccine efficacy in the second year of life owing to a low number of events among older children, potential bias due to censoring of placebo children at the time of study vaccine receipt, and suboptimal adapted severity scoring based on the Vesikari score, which was designed for use in settings with high parental literacy.ConclusionsRotasiil provided protection against SRVGE in infants through an extended follow-up period of approximately 2 years. Protection was significant in the first year of life, when the disease burden and risk of death are highest, and against a changing pattern of rotavirus strains during the 2-year efficacy period. Rotavirus vaccines that are safe, effective, and protective against multiple strains represent the best hope for preventing the severe consequences of rotavirus infection, especially in resource-limited settings, where access to care may be limited. Studies such as this provide valuable information for the planning of national immunization programs and future vaccine development.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02145000","term_id":"NCT02145000"}}NCT02145000.

Sheila Isanaka and co-workers report extended follow-up of a rotavirus vaccine trial in Niger.     

A guinea fowl genome assembly provides new evidence on evolution following domestication and selection in galliformes

The helmeted guinea fowl Numida meleagris belongs to the order Galliformes. Its natural range includes a large part of sub‐Saharan Africa, from Senegal to Eritrea and from Chad to South Africa. Archaeozoological and artistic evidence suggest domestication of this species may have occurred about 2,000 years BP in Mali and Sudan primarily as a food resource, although villagers also benefit from its capacity to give loud alarm calls in case of danger, of its ability to consume parasites such as ticks and to hunt snakes, thus suggesting its domestication may have resulted from a commensal association process. Today, it is still farmed in Africa, mainly as a traditional village poultry, and is also bred more intensively in other countries, mainly France and Italy. The lack of available molecular genetic markers has limited the genetic studies conducted to date on guinea fowl. We present here a first‐generation whole‐genome sequence draft assembly used as a reference for a study by a Pool‐seq approach of wild and domestic populations from Europe and Africa. We show that the domestic populations share a higher genetic similarity between each other than they do to wild populations living in the same geographical area. Several genomic regions showing selection signatures putatively related to domestication or importation to Europe were detected, containing candidate genes, most notably EDNRB2, possibly explaining losses in plumage coloration phenotypes in domesticated populations.     

Fine mapping of <Emphasis Type="Italic">RYMV3</Emphasis>: a new resistance gene to <Emphasis Type="Italic">Rice yellow mottle virus</Emphasis> from <Emphasis Type="Italic">Oryza glaberrima</Emphasis>

Key message

A new resistance gene against Rice yellow mottle virus was identified and mapped in a 15-kb interval. The best candidate is a CC-NBS-LRR gene.

Abstract

Rice yellow mottle virus (RYMV) disease is a serious constraint to the cultivation of rice in Africa and selection for resistance is considered to be the most effective management strategy. The aim of this study was to characterize the resistance of Tog5307, a highly resistant accession belonging to the African cultivated rice species (Oryza glaberrima), that has none of the previously identified resistance genes to RYMV. The specificity of Tog5307 resistance was analyzed using 18 RYMV isolates. While three of them were able to infect Tog5307 very rapidly, resistance against the others was effective despite infection events attributed to resistance-breakdown or incomplete penetrance of the resistance. Segregation of resistance in an interspecific backcross population derived from a cross between Tog5307 and the susceptible Oryza sativa variety IR64 showed that resistance is dominant and is controlled by a single gene, named RYMV3. RYMV3 was mapped in an approximately 15-kb interval in which two candidate genes, coding for a putative transmembrane protein and a CC-NBS-LRR domain-containing protein, were annotated. Sequencing revealed non-synonymous polymorphisms between Tog5307 and the O. glaberrima susceptible accession CG14 in both candidate genes. An additional resistant O. glaberrima accession, Tog5672, was found to have the Tog5307 genotype for the CC-NBS-LRR gene but not for the putative transmembrane protein gene. Analysis of the cosegregation of Tog5672 resistance with the RYMV3 locus suggests that RYMV3 is also involved in Tog5672 resistance, thereby supporting the CC-NBS-LRR gene as the best candidate for RYMV3.

     

An effective method to purify Plasmodium falciparum DNA directly from clinical blood samples for whole genome high-throughput sequencing

Highly parallel sequencing technologies permit cost-effective whole genome sequencing of hundreds of Plasmodium parasites. The ability to sequence clinical Plasmodium samples, extracted directly from patient blood without a culture step, presents a unique opportunity to sample the diversity of "natural" parasite populations in high resolution clinical and epidemiological studies. A major challenge to sequencing clinical Plasmodium samples is the abundance of human DNA, which may substantially reduce the yield of Plasmodium sequence. We tested a range of human white blood cell (WBC) depletion methods on P. falciparum-infected patient samples in search of a method displaying an optimal balance of WBC-removal efficacy, cost, simplicity, and applicability to low resource settings. In the first of a two-part study, combinations of three different WBC depletion methods were tested on 43 patient blood samples in Mali. A two-step combination of Lymphoprep plus Plasmodipur best fitted our requirements, although moderate variability was observed in human DNA quantity. This approach was further assessed in a larger sample of 76 patients from Burkina Faso. WBC-removal efficacy remained high (<30% human DNA in >70% samples) and lower variation was observed in human DNA quantities. In order to assess the Plasmodium sequence yield at different human DNA proportions, 59 samples with up to 60% human DNA contamination were sequenced on the Illumina Genome Analyzer platform. An average ~40-fold coverage of the genome was observed per lane for samples with ≤ 30% human DNA. Even in low resource settings, using a simple two-step combination of Lymphoprep plus Plasmodipur, over 70% of clinical sample preparations should exhibit sufficiently low human DNA quantities to enable ~40-fold sequence coverage of the P. falciparum genome using a single lane on the Illumina Genome Analyzer platform. This approach should greatly facilitate large-scale clinical and epidemiologic studies of P. falciparum.